Understanding the regulation of coronary blood flow is important to future basic studies of the myocardium. However, these studies will have more than a theoretical interest since the metabolic and adrenergic activities of the myocardium have important implications in many facets of coronary disease. The overall aim of this study is to evaluate the interaction of adenosine with adrenergic activity in the regulation of coronary vascular resistance. The principal objectives of this proposal are: 1) analyze the relationship between local vasoactive metabolite production, primarily adenosine, and catecholamine release as related to changes in coronary vascular resistance, 2) compare metabolic and hemodynamic changes in the intact innervated hearts, alpha-receptor and beta-receptor blocked hearts and chemically denervated hearts and, 3) in the anesthetized dog model, evaluated transmural coronary blood flow, adenosine content and catecholamine content in innervated, adrevergic blocked, and denervated hearts. In the anesthetized dog model, evaluate transmural coronary blood flow, adenosine content and catecholamine content in innervated, adrenergic blocked, and denervated hearts. In the unanesthetized chronic dog preparation, the regulation of coronary blood flow will be studied by changing the neural activity with either alpha receptor blockade, beta-receptor blockage, or chemical denervation. In the same animals metabolic activity will be changed by graded changes in cardiac work produced by treadmill exercise. Hemodynamic parameters including: intraventricular pressure, dP/dt, arterial blood pressure, and coronary blood flow will be monitored while blood samples are drawn for metabolite concentration in arterial and coronary sinus blood. Measurements of oxygen content, pH, lactate and pyruvate will enable us to assess the metabolic state of the myocardium. Changes in V-A adenosine concentrations will allow us to estimate the adenosine concentration at the vascular smooth muscle. Catecholamine release will provide evidence of the sympathetic activity of the myocardium. In the open-chest anesthetized dog preparation transmural adenosine content, catecholamine content and uptake will be related to transmural coronary blood flow. Using alpha-receptor blockage, beta-receptor blockage and cardiac denervation we will study the transmural control of coronary blood flow. These studies will lead to a better undestanding of the interaction between the local metabolic control and the neural control of the coronary circulation.